The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 +/- 1.1 pg/mL; MSV = 12.8 +/- 1.2 pg/mL), TNF-alpha (FSV = 16.6 +/- 1.2 pg/mL; MSV = 12.8 +/- 1 pg/mL) and IL-6 (FSV = 10.3 +/- 0.2 pg/mL; MSV = 7.2 +/- 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-alpha) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. in conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.Univ Fed Espirito Santo, Dept Ciencias Fisiol, BR-29042755 Vitoria, ES, BrazilInst Fed Espirito Santo, Vitoria, ES, BrazilCtr Univ Vila Velha, Dept Farm, Vila Velha, ES, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilWeb of Scienc

Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP

Vasodilator response to increasing concentrations of bradykinin (BK: 0.1–1,000 ng).

<p>Before (A) and after inhibition with L-NAME (B), indomethacin (INDO) (C); L-NAME + INDO (D), and L-NAME + INDO + clotrimazole (E). The values are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, +p<0.05 compared with the PHYSIO group, and §p <0.05 compared with the SUPRA group.</p

Systolic blood pressure of normotensive rats.

<p>SHAM (n = 15), CAST (n = 15), PHYSIO (n = 21), and SUPRA (n = 15) groups. The values are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, and +p <0.05 compared with the PHYSIO group.</p

Body weight and relationship of the dry weight of the heart chambers with body weight in the SHAM, CAST, SUPRA, and PHYSIO groups after 15 days of treatment with testosterone.

<p>The values are expressed as the mean ± SEM.</p><p>* p<0.05 compared with the SHAM group.</p><p>Body weight and relationship of the dry weight of the heart chambers with body weight in the SHAM, CAST, SUPRA, and PHYSIO groups after 15 days of treatment with testosterone.</p

Coronary perfusion pressure (CPP, mmHg) in normotensive rats after inhibition with 100 μM L-NAME, 28 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole.

<p>The values are expressed as the mean ± SEM.</p><p>* p<0.05 compared with the respective controls.</p><p>Coronary perfusion pressure (CPP, mmHg) in normotensive rats after inhibition with 100 μM L-NAME, 28 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole.</p

Baseline coronary perfusion pressure (CPP) of normotensive rats.

<p>SHAM (n = 20), CAST (n = 23), PHYSIO (n = 20), and SUPRA (n = 23) groups. The values are expressed as the mean ± SEM.</p

Hormone level.

<p>Testosterone in the SHAM (n = 15), CAST (n = 15); PHYSIO (n = 17), and SUPRA (n = 16) groups. Data are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, and +p<0.05 compared with the PHYSIO group.</p

Lipid profile of normotensive rats.

<p>A) Triglycerides, B) total cholesterol, C) very-low-density lipoproteins (VLDL), D) low-density lipoprotein (LDL) cholesterol, and E) high-density lipoprotein (HDL) cholesterol in the SHAM (n = 15), CAST (n = 17), PHYSIO (n = 17), and SUPRA (n = 16) groups. Data are expressed as the mean ± SEM. *p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group.</p

Fatores de risco cardiovasculares, suas associações e presença de síndrome metabólica em adolescentes Cardiovascular risk factors, their associations and presence of metabolic syndrome in adolescents

OBJETIVO: Avaliar a ocorrência de síndrome metabólica (SM) e fatores de risco associados em adolescentes de Vitória (ES). MÉTODOS: Foram avaliados 380 adolescentes de 10 a 14 anos de idade estudantes de escolas públicas. Foram mensurados: índice de massa corporal, pressão arterial em repouso, dosagens séricas em jejum das concentrações de colesterol total, LDL-colesterol, HDL-colesterol, triglicerídeos e glicose. RESULTADOS: Identificou-se prevalência de sobrepeso em 9,6% dos meninos e em 7,4% das meninas, enquanto que obesidade foi observada em 6,2 e 4,9%, respectivamente. As concentrações de triglicerídeos foram limítrofes ou altas em 6,8 e 3,4% dos meninos e em 11,8 e 5,9% das meninas. A concentração de HDL-colesterol estava abaixo dos níveis padronizados em 8,5% dos meninos e em 9,9% das meninas. A pressão arterial em repouso foi limítrofe para 5,1% dos meninos e 7,9% das meninas, enquanto que 3,4% tanto dos meninos quanto das meninas foram considerados hipertensos. Glicemia de jejum foi alta em 0,6% dos meninos e em 0,5% das meninas. No grupo estudado, 2,8% dos meninos e 2,5% das meninas apresentaram dois fatores de risco associados a SM. A prevalência de SM foi de 1,1% para meninos e 1,5% para meninas e a total foi de 1,3%. CONCLUSÕES: Fatores de risco cardiovasculares associados a SM são condições clínicas importantes nessa faixa etária. Um número significativo de adolescentes apresentou resultados limítrofes, os quais podem aumentar a prevalência de SM ou de fatores de risco independentes em curto prazo. Mais investimentos devem ser feitos na prevenção primária, considerando que o diagnóstico precoce é uma questão de fundamental importância.<br>OBJECTIVE: To evaluate the occurrence of metabolic syndrome (MS) and independent associated risk factors in adolescents in the city of Vitória, Brazil. METHODS: We assessed 380 adolescents aged 10 to 14 years attending public schools. Body mass index and blood pressure at rest were measured. Fasting plasma concentrations of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose were also obtained. RESULTS: The prevalence of overweight was 9.6% for boys and 7.4% for girls, while obesity was found in 6.2 and 4.9%, respectively. Triglyceride concentrations were borderline or high in 6.8 and 3.4% of the boys and in 11.8 and 5.9% of the girls. HDL-cholesterol was below recommended levels in 8.5% of the boys and in 9.9% of the girls. Blood pressure at rest was borderline for 5.1% of the boys and 7.9% of the girls, while 3.4% of both boys and girls were hypertensive. Fasting glycemia was high in 0.6% of the boys and in 0.5% of the girls. In the group studied, 2.8% of the boys and 2.5% of the girls had two risk factors associated with MS. Prevalence of MS was 1.1% for boys and 1.5% for girls, and overall prevalence was 1.3%. CONCLUSIONS: MS and associated cardiovascular risk factors are serious clinical conditions in this age group. A significant number of adolescents showed borderline results, which may increase the prevalence of MS or independent risk factors in the short term. More investments should be made in primary prevention, considering that early diagnosis is an issue of fundamental importance